Sadullah Keles1, Zekai Halici2, Hasan Tarik Atmaca3, Muhammed Yayla2, Kenan Yildirim4, Metin Ekinci5, Erol Akpinar2, Durdu Altuner6, Ozgur Cakici7, Zafer Bayraktutan8. 1. Department of Ophthalmology, Faculty of Medicine, Ataturk University, Erzurum, Turkey. 2. Department of Pharmacology, Faculty of Medicine, Ataturk University, Erzurum, Turkey. 3. Department of Pathology, Faculty of Veterinary, Kırıkkale University, Kırıkkale, Turkey. 4. Department of Ophthalmology, Igdır Government Hospital, Igdır, Turkey. 5. Department of Ophthalmology, Faculty of Medicine, Kafkas University, Kars, Turkey. 6. Department of Pharmacology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize, Turkey. 7. Department of Ophthalmology, Mugla Sıtkı Kocaman University, Faculty of Medicine, Mugla, Turkey. 8. Department of Biochemistry, Regional Research and Education Hospital, Erzurum, Turkey.
Abstract
PURPOSE: We compared the anti-inflammatory effects of bosentan and dexamethasone in endotoxin-induced uveitis (EIU). METHODS: Endotoxin-induced uveitis was induced by subcutaneous injection of lipopolysaccharide (LPS, 200 μg) in Wistar rats. Rats were divided randomly into 10 groups (n = 6). Bosentan at doses of 50 and 100 mg/kg were administered orally 1 hour before and 12 hours after LPS injection, and dexamethasone was administered by intraperitoneally 30 minutes before and 30 minutes after LPS injection at a dose of 1 mg/kg. Data were collected at two time points for each control and treatment; animals were killed at either 3 or 24 hours after LPS injection. Histopathologic evaluation and aqueous humour measurements of TNF-α level were performed, and endothelin-1 (ET-1), inducible nitric oxide synthase (iNOS), and endothelin receptor A and B (EDNRA and B) expression were analyzed. RESULTS: The group treated with 100 mg/kg bosentan at 24 hours displayed significantly milder uveitis and fewer inflammatory cells compared to LPS-injected animals, and there were similar findings in the dexamethasone-treated group at 24 hours. The TNF-α levels in the dexamethasone treatment group were lower than those in the LPS-induced uveitis control group (P < 0.05); however, there was no difference between the dexamethasone and bosentan treatment groups at 3 and 24 hours after LPS administration. Bosentan treatment at doses of 50 and 100 mg/kg significantly decreased iNOS expression compared to LPS-injected animals (P < 0.001). The ET-1 expression was suppressed significantly by bosentan and dexamethasone at 3 and 24 hours after LPS administration (P < 0.001). The EDNRA expression in the bosentan treatment groups was statistically significantly lower than that in the LPS-induced uveitis control group at 3 and 24 hours after LPS administration (P < 0.05). CONCLUSIONS: Bosentan reduces intraocular inflammation and has similar effects as dexamethasone in a rat model of EIU. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
PURPOSE: We compared the anti-inflammatory effects of bosentan and dexamethasone in endotoxin-induced uveitis (EIU). METHODS: Endotoxin-induced uveitis was induced by subcutaneous injection of lipopolysaccharide (LPS, 200 μg) in Wistar rats. Rats were divided randomly into 10 groups (n = 6). Bosentan at doses of 50 and 100 mg/kg were administered orally 1 hour before and 12 hours after LPS injection, and dexamethasone was administered by intraperitoneally 30 minutes before and 30 minutes after LPS injection at a dose of 1 mg/kg. Data were collected at two time points for each control and treatment; animals were killed at either 3 or 24 hours after LPS injection. Histopathologic evaluation and aqueous humour measurements of TNF-α level were performed, and endothelin-1 (ET-1), inducible nitric oxide synthase (iNOS), and endothelin receptor A and B (EDNRA and B) expression were analyzed. RESULTS: The group treated with 100 mg/kg bosentan at 24 hours displayed significantly milder uveitis and fewer inflammatory cells compared to LPS-injected animals, and there were similar findings in the dexamethasone-treated group at 24 hours. The TNF-α levels in the dexamethasone treatment group were lower than those in the LPS-induced uveitis control group (P < 0.05); however, there was no difference between the dexamethasone and bosentan treatment groups at 3 and 24 hours after LPS administration. Bosentan treatment at doses of 50 and 100 mg/kg significantly decreased iNOS expression compared to LPS-injected animals (P < 0.001). The ET-1 expression was suppressed significantly by bosentan and dexamethasone at 3 and 24 hours after LPS administration (P < 0.001). The EDNRA expression in the bosentan treatment groups was statistically significantly lower than that in the LPS-induced uveitis control group at 3 and 24 hours after LPS administration (P < 0.05). CONCLUSIONS:Bosentan reduces intraocular inflammation and has similar effects as dexamethasone in a rat model of EIU. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
Authors: Karla G G Serafim; Suelen A Navarro; Ana C Zarpelon; Felipe A Pinho-Ribeiro; Victor Fattori; Thiago M Cunha; Jose C Alves-Filho; Fernando Q Cunha; Rubia Casagrande; Waldiceu A Verri Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2015-08-06 Impact factor: 3.000